Acta Medica Okayama. A comparison of the signal pathways between the TNF alpha- and oridonin-induced murine L929 fibrosarcoma cell death.

Transcription

1 Acta Medica Okayama Volume 59, Issue Article 4 DECEMBER 2005 A comparison of the signal pathways between the TNF alpha- and oridonin-induced murine L929 fibrosarcoma cell death. Jian Huang Lijun Wu Shin-ichi Tashiro Satoshi Onodera Takashi Ikejima Shenyang Pharmaceutical University, Shenyang Pharmaceutical University, Showa Pharmaceutical University, Showa Pharmaceutical University, Shenyang Pharmaceutical University, Copyright c 1999 OKAYAMA UNIVERSITY MEDICAL SCHOOL. All rights reserved.

2 A comparison of the signal pathways between the TNF alpha- and oridonin-induced murine L929 fibrosarcoma cell death. Jian Huang, Lijun Wu, Shin-ichi Tashiro, Satoshi Onodera, and Takashi Ikejima Abstract Oridonin, an active component isolated from Rabdosia rubescences, has been reported to have antitumor effects. In this study, we compared the signal transduction pathways between TNFalpha-and oridonin-induced L929 cell death. Oridonin and TNFalpha initiated apoptotic morphologic changes, but DNA fragmentation was found in TNFalpha-treated L929 cells but not in oridonin-treated ones. The pan-caspase inhibitor (z-vad-fmk), caspase-8 inhibitor (z- IETD-fmk) and caspase-3 inhibitor (z-devd-fmk) augmented oridonin-and TNFalpha-induced cell death. However, the caspase-9 inhibitor (z-lehd-fmk) only increased oridonin-induced L929 cell death. Moreover, poly (ADPribose) polymerase (PARP) was cleaved in oridonin-treated L929 cells but not in the TNFalpha-treated groups, and the caspase-3 inhibitor (z-devd-fmk) failed to inhibit PARP cleavage. These results showed that only oridonin-induced L929 cell death required PARP degradation in a caspase-3 independent manner. In addition, oridonin increased the ratio of Bax/Bcl-2 protein expression, but TNFalpha did not. TNFalpha induced p38 and ERK activation, whereas oridonin triggered only ERK activation. We also investigated the effect of oridonin on intracellular TNFalpha expression, and found that oridonin augmented endogenous pro-tnfalpha expression and its upstream protein IkB phosphorylation. These results indicated that although oridonin promoted endogenous pro-tnfalpha expression, a great difference existed between the signal pathways through which TNFalpha-and oridonin-induced cell death. KEYWORDS: oridonin, caspase, Bax/Bcl-2, MAPK, I?B PMID: [PubMed - indexed for MEDLINE] Copyright (C) OKAYAMA UNIVERSITY MEDICAL SCHOOL

3 Huang et al.: A comparison of the signal pathways between the TNF Produced by The Berkeley Electronic Press,

4 Acta Medica Okayama, Vol. 59 [2005], Iss. 6, Art

5 Huang et al.: A comparison of the signal pathways between the TNF Produced by The Berkeley Electronic Press,

6 Acta Medica Okayama, Vol. 59 [2005], Iss. 6, Art

7 Huang et al.: A comparison of the signal pathways between the TNF Produced by The Berkeley Electronic Press,

8 Acta Medica Okayama, Vol. 59 [2005], Iss. 6, Art

9 Huang et al.: A comparison of the signal pathways between the TNF Produced by The Berkeley Electronic Press,

10 Acta Medica Okayama, Vol. 59 [2005], Iss. 6, Art

11 Huang et al.: A comparison of the signal pathways between the TNF Produced by The Berkeley Electronic Press,

12 Acta Medica Okayama, Vol. 59 [2005], Iss. 6, Art